Mobilized hematopoietic stem cell yield depends on species-specific circadian timing.
Endogenous rhythmicity likely evolved as a mechanism allowing organisms to anticipate predictable daily changes in the environment (Rutter et al., 2002). Under homeostasis, murine hematopoietic stem cell (HSC) egress is orchestrated by rhythmic beta 3 adrenergic signals delivered by the sympathetic nervous system (SNS) that regulate Cxcl12 expression in stromal cells (Mendez-Ferrer et al., 2008). Here, we show that CXCR4 is also regulated under circadian control whose rhythm is synchronized with its ligand, CXCL12, to optimize HSC trafficking. These circadian oscillations are inverted in humans compared to the mouse and continue to influence the yield even when stem cell mobilization is enforced. Our results suggest that the human HSC yield for clinical transplantation might be significantly greater if patients were harvested during the evening compared to the morning.
Lucas
Daniel
D
Battista
Michela
M
Shi
Patricia A
PA
Isola
Luis
L
Frenette
Paul S
PS
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001596:Benzylamines; D001781:Blood Component Removal; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D000080027:Cyclams; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D055786:Gene Knockout Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D016179:Granulocyte Colony-Stimulating Factor; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C514936:CXCR4 protein, mouse; C515256:Cxcl12 protein, mouse; C088327:plerixafor